High Erythrocyte Mean Corpuscular Volume Predicts Methotrexate Response in PsA

Hand psoriatic arthritis
Hand psoriatic arthritis
Researchers investigated the generalizability of a previous study finding that increased mean corpuscular volume complements clinical response in psoriatic arthritis.

Increased erythrocyte mean corpuscular volume (MCV) 12 weeks after methotrexate (MTX) initiation is predictive of treatment response in patients with psoriatic arthritis (PsA), according to study results published in Rheumatology (Oxford).

Treatment-naive adult patients with PsA who fulfilled the classification criteria for PsA (CASPAR) were enrolled in the study. Data extraction occurred in June 2020 from 2 independent cohorts in which MTX treatment was initiated between January 2014 and December 2019.

Study patients in cohort 1 were selected from University College London Hospital (n=128) and those in cohort 2 were enrolled in the study from North Middlesex University Hospital (n=42).

Response at 24 weeks was defined as “an improvement in at least 2 of the 4 PsA Response Criteria (PsARC),” one of which must be related to “joint tenderness or swelling, with no worsening in any of the 4 criteria, and no initiation of additional conventional synthetic disease-modifying antirheumatic drugs or biologics” within 52 weeks of MTX initiation.

Overall, 74 of the total 170 study patients with PsA (43.5%) responded to MTX based on PsARC criteria. The mean participant age at PsA onset was 47±15 years, and the mean duration of disease was 10.5±6 months; 42% of the patients were men. The median MTX dose at treatment initiation was 10 mg/week (range, 7.5-10 mg/week), which increased to 15 mg/week (range, 12.5-17.5 mg/week) at 12 weeks, and to 17.5 mg/week (range, 15-20 mg/week) at 24 weeks.

After 12 weeks, a significant increase in MCV was observed among responders compared with nonresponders (difference in MCV, 1.66 fL; 95% CI, 0.42-2.89 fL; P =.009). The earliest point at which the area under the receiver operator characteristic curve (AUROC) was greater than 0.70. This was chosen for the logistic regression model to assess MCV as a predictor of response adjusted by other parameters. 

Change in MCV at 12 weeks was the best performing positive predictor of response at 24 weeks by sparse partial least squares discriminant analysis, which was followed by PsARC response at 12 weeks and the presence of dactylitis. For every 1-fL increase in MCV at 12 weeks from baseline, the odds ratio (OR) of achieving a response by 24 weeks increased by 1.27 (95% CI, 1.12-1.46; P <.001).

The optimal cutoff point for MCV increment to predict a response at 12 weeks was 3.9 fL or greater (95% CI, 2.6-4.2. fL; AUROC, 0.71). The OR of attaining a favorable response at 24 weeks was 2.97 (95% CI, 1.49-5.95; P =.002) if the participants demonstrated a PsARC response at 12 weeks (AUROC, 0.65). A PsARC response at 12 weeks and an increase in MCV of 3.9 or less at 12 weeks together improved the AUROC to predict a response at 24 weeks to 0.80.

Overall, 27 of 28 study patients (96%) with an elevated MCV of at least 3.9 who attained a 12-week PsARC response responded at 24 weeks. The presence of dactylitis was linked to a significantly favorable response to MTX (OR, 3.34; 95% CI, 1.34-7.17; P =.010).

The study authors concluded, “[P]rospective studies designed to evaluate the utility of early changes in MCV in predicting response to MTX among patients with PsA are warranted.”


Shipa MRA, Langley L, Sacks B, et al. Increased erythrocyte mean corpuscular volume by methotrexate predicts clinical response in psoriatic arthritis. Rheumatology (Oxford). Published online May 9, 2022. doi:10.1093/rheumatology/keac276